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TWNK twinkle mtDNA helicase [ Homo sapiens (human) ]

Gene ID: 56652, updated on 5-Mar-2024

Summary

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Official Symbol
TWNKprovided by HGNC
Official Full Name
twinkle mtDNA helicaseprovided by HGNC
Primary source
HGNC:HGNC:1160
See related
Ensembl:ENSG00000107815 MIM:606075; AllianceGenome:HGNC:1160
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PEO; PEO1; SCA8; ATXN8; IOSCA; PEOA3; SANDO; TWINL; MTDPS7; PRLTS5; C10orf2
Summary
This gene encodes a hexameric DNA helicase which unwinds short stretches of double-stranded DNA in the 5' to 3' direction and, along with mitochondrial single-stranded DNA binding protein and mtDNA polymerase gamma, is thought to play a key role in mtDNA replication. The protein localizes to the mitochondrial matrix and mitochondrial nucleoids. Mutations in this gene cause infantile onset spinocerebellar ataxia (IOSCA) and progressive external ophthalmoplegia (PEO) and are also associated with several mitochondrial depletion syndromes. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Aug 2009]
Expression
Ubiquitous expression in testis (RPKM 6.0), lymph node (RPKM 3.3) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
10q24.31
Exon count:
5
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (100987543..100994403)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (101870918..101877778)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (102747300..102754160)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene semaphorin 4G Neighboring gene microRNA 608 Neighboring gene mitochondrial ribosomal protein L43 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3902 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:102755784-102756653 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2712 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2713 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2714 Neighboring gene leucine zipper tumor suppressor 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:102768034-102768715 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:102768716-102769396 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3904 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3905 Neighboring gene PDZ domain containing 7 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3906 Neighboring gene sideroflexin 3

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The N-terminal domain of human mitochondrial helicase Twinkle has DNA-binding activity crucial for supporting processive DNA synthesis by polymerase γ. Johnson LC, et al. J Biol Chem, 2023 Jan. PMID 36528058, Free PMC Article
  2. Structural insight and characterization of human Twinkle helicase in mitochondrial disease. Riccio AA, et al. Proc Natl Acad Sci U S A, 2022 Aug 9. PMID 35914129, Free PMC Article
  3. Characteristics of globus pallidus internus local field potentials in generalized dystonia patients with TWNK mutation. Zhu GY, et al. Clin Neurophysiol, 2020 Jul. PMID 32387964
  4. Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase. Kaur P, et al. J Biol Chem, 2020 Apr 24. PMID 32213598, Free PMC Article
  5. Perrault syndrome with neurological features in a compound heterozygote for two TWNK mutations: overlap of TWNK-related recessive disorders. Domínguez-Ruiz M, et al. J Transl Med, 2019 Aug 28. PMID 31455392, Free PMC Article

See all (126) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The N-terminal domain of human mitochondrial helicase Twinkle has DNA-binding activity crucial for supporting processive DNA synthesis by polymerase gamma.
    Title: The N-terminal domain of human mitochondrial helicase Twinkle has DNA-binding activity crucial for supporting processive DNA synthesis by polymerase γ.
  2. Structural insight and characterization of human Twinkle helicase in mitochondrial disease.
    Title: Structural insight and characterization of human Twinkle helicase in mitochondrial disease.
  3. Progressive External Ophthalmoplegia in Polish Patients-From Clinical Evaluation to Genetic Confirmation.
    Title: Progressive External Ophthalmoplegia in Polish Patients-From Clinical Evaluation to Genetic Confirmation.
  4. Clinical, pathological and genetic spectrum in 89 cases of mitochondrial progressive external ophthalmoplegia.
    Title: Clinical, pathological and genetic spectrum in 89 cases of mitochondrial progressive external ophthalmoplegia.
  5. Stimulation of Variant Forms of the Mitochondrial DNA Helicase Twinkle by the Mitochondrial Single-Stranded DNA-Binding Protein.
    Title: Stimulation of Variant Forms of the Mitochondrial DNA Helicase Twinkle by the Mitochondrial Single-Stranded DNA-Binding Protein.
  6. Characteristics of globus pallidus internus local field potentials in generalized dystonia patients with TWNK mutation.
    Title: Characteristics of globus pallidus internus local field potentials in generalized dystonia patients with TWNK mutation.
  7. Consequences of compromised mitochondrial genome integrity.
    Title: Consequences of compromised mitochondrial genome integrity.
  8. Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase.
    Title: Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase.
  9. patients with Perrault syndrome caused by TWNK mutations will manifest neurological signs in adulthood.
    Title: Perrault syndrome with neurological features in a compound heterozygote for two TWNK mutations: overlap of TWNK-related recessive disorders.
  10. Two novel TWNK c.1186 C > T/ c.1844 G > C compound heterozygous mutations which were probably the disease-causing mutations of hepatocerebral form of Mitochondrial DNA depletion syndrome (MDS) and described the clinical manifestations of the proband, which expanded the phenotypic spectrum of MDS caused by variants in TWNK.
    Title: Whole exome sequencing reveals two novel compound heterozygous mutations in TWNK as a cause of the hepatocerebral form of mitochondrial DNA depletion syndrome: a case report.
Submit: New GeneRIF Correction See all GeneRIFs (61)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ21832

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 5'-3' DNA helicase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables ATP hydrolysis activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables DNA helicase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables isomerase activity IEA
Inferred from Electronic Annotation
more info
  
enables lipid binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protease binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables single-stranded DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables single-stranded DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in DNA unwinding involved in DNA replication IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to glucose stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in mitochondrial DNA replication IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in mitochondrial DNA replication IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in mitochondrial DNA replication NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in mitochondrial transcription IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein hexamerization IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in mitochondrial inner membrane IEA
Inferred from Electronic Annotation
more info
  
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
located_in mitochondrial nucleoid IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
twinkle mtDNA helicase
Names
T7 gp4-like protein with intramitochondrial nucleoid localization
T7 helicase-related protein with intramitochondrial nucleoid localization
T7-like mitochondrial DNA helicase
ataxin 8
progressive external ophthalmoplegia 1 protein
twinkle protein, mitochondrial
NP_001157284.1
NP_001157285.1
NP_001157286.1
NP_001355204.1
NP_068602.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_012624.1 RefSeqGene

    Range
    5008..11868
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001163812.2 → NP_001157284.1  twinkle mtDNA helicase isoform B

    See identical proteins and their annotated locations for NP_001157284.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region which introduces a novel stop codon, compared to variant 1. The encoded protein (isoform B; also known as Twinky) has a shorter and distinct C-terminus, which lacks a C-terminal domain required for hexamer formation, compared to isoform A.
    Source sequence(s)
    AF292005, AK025485, AL133215, BC013349, DB090322
    Consensus CDS
    CCDS53570.1
    UniProtKB/Swiss-Prot
    Q96RR1
    UniProtKB/TrEMBL
    Q9H6V3
    Related
    ENSP00000359248.1, ENST00000370228.2
    Conserved Domains (2) summary
    cd01029
    Location:259 → 335
    TOPRIM_primases; TOPRIM_primases: The topoisomerase-primase (TORPIM) nucleotidyl transferase/hydrolase domain found in the active site regions of bacterial DnaG-type primases and their homologs. Primases synthesize RNA primers for the initiation of DNA replication. DnaG ...
    cl21455
    Location:374 → 580
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

  2. NM_001163813.2 → NP_001157285.1  twinkle mtDNA helicase isoform C

    See identical proteins and their annotated locations for NP_001157285.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate splice site in exon 1 that results in the use of an in-frame downstream start codon, compared to variant 1. The encoded protein (isoform C) lacks most of the N-terminus, which contains a mitochondrial targeting sequence and probable ssDNA binding domain, compared to isoform A.
    Source sequence(s)
    AK025485, AL133215, BQ643363, CB112401
    Consensus CDS
    CCDS86136.1
    UniProtKB/TrEMBL
    A0A2R8Y4V4, B4DLM7
    Related
    ENSP00000494326.1, ENST00000473656.5
    Conserved Domains (1) summary
    cd01122
    Location:1 → 175
    Twinkle_C; C-terminal domain of Twinkle

  3. NM_001163814.2 → NP_001157286.1  twinkle mtDNA helicase isoform D

    See identical proteins and their annotated locations for NP_001157286.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) has multiple splice site differences, compared to variant 1. The encoded protein (isoform D) lacks most of the N-terminus, which contains a mitochondrial targeting sequence and probable ssDNA binding domain, and has a shorter and distinct C-terminus, which lacks a C-terminal domain required for hexamer formation, compared to isoform A.
    Source sequence(s)
    AK025485, AL133215, CB112401
    Consensus CDS
    CCDS86137.1
    UniProtKB/TrEMBL
    A0A2R8Y746
    Related
    ENSP00000496012.1, ENST00000476766.5
    Conserved Domains (1) summary
    cl38936
    Location:1 → 126
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

  4. NM_001368275.1 → NP_001355204.1  twinkle mtDNA helicase isoform C

    Status: REVIEWED

    Source sequence(s)
    AL133215
    Consensus CDS
    CCDS86136.1
    UniProtKB/TrEMBL
    A0A2R8Y4V4, B4DLM7
    Conserved Domains (1) summary
    cd01122
    Location:1 → 175
    Twinkle_C; C-terminal domain of Twinkle

  5. NM_021830.5 → NP_068602.2  twinkle mtDNA helicase isoform A

    See identical proteins and their annotated locations for NP_068602.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (A; also known as Twinkle).
    Source sequence(s)
    AF292004, AK025485, AL133215, DB090322
    Consensus CDS
    CCDS7506.1
    UniProtKB/Swiss-Prot
    B2CQL2, Q6MZX2, Q6PJP5, Q96RR0, Q96RR1
    UniProtKB/TrEMBL
    E5KSY5
    Related
    ENSP00000309595.2, ENST00000311916.8
    Conserved Domains (2) summary
    cd01029
    Location:259 → 335
    TOPRIM_primases; TOPRIM_primases: The topoisomerase-primase (TORPIM) nucleotidyl transferase/hydrolase domain found in the active site regions of bacterial DnaG-type primases and their homologs. Primases synthesize RNA primers for the initiation of DNA replication. DnaG ...
    cd01122
    Location:374 → 632
    GP4d_helicase; GP4d_helicase is a homohexameric 5'-3' helicases. Helicases couple NTP hydrolysis to the unwinding of nucleic acid duplexes into their component strands.

RNA

  1. NR_160738.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL133215
    Related
    ENST00000643860.1

  2. NR_160739.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL133215

  3. NR_160740.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL133215

  4. NR_160741.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL133215

  5. NR_160742.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL133215

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

    Range
    100987543..100994403
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    101870918..101877778
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q96RR1.1 GenPept UniProtKB/Swiss-Prot:Q96RR1

Gene LinkOut

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